Variant 13-28713313-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181785.4(SLC46A3):c.427A>G(p.Asn143Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,613,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SLC46A3
NM_181785.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.39

Variant links:

Genes affected

SLC46A3 (HGNC:27501): (solute carrier family 46 member 3) The protein encoded by this gene is a member of a transmembrane protein family that transports small molecules across membranes. The encoded protein has been found in lysosomal membranes, where it can transport catabolites from the lysosomes to the cytoplasm. This protein has been shown to be an effective transporter of the cytotoxic drug maytansine, which is used in antibody-based targeting of cancer cells. [provided by RefSeq, Dec 2016]

SLC46A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049015015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC46A3	NM_181785.4 linkuse as main transcript	c.427A>G	p.Asn143Asp	missense_variant	3/6	ENST00000266943.11	NP_861450.1	Q7Z3Q1-1A0A024RDN9
SLC46A3	NM_001135919.2 linkuse as main transcript	c.427A>G	p.Asn143Asp	missense_variant	3/7		NP_001129391.1	Q7Z3Q1-2
SLC46A3	NM_001347960.2 linkuse as main transcript	c.427A>G	p.Asn143Asp	missense_variant	3/6		NP_001334889.1	Q7Z3Q1-1A0A024RDN9
SLC46A3	XM_005266361.3 linkuse as main transcript	c.427A>G	p.Asn143Asp	missense_variant	3/7		XP_005266418.1	Q7Z3Q1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC46A3	ENST00000266943.11 linkuse as main transcript	c.427A>G	p.Asn143Asp	missense_variant	3/6	1	NM_181785.4	ENSP00000266943.7		Q7Z3Q1-1
SLC46A3	ENST00000380814.4 linkuse as main transcript	c.427A>G	p.Asn143Asp	missense_variant	3/7	1		ENSP00000370192.4		Q7Z3Q1-2

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000638

AC:

AN:

250702

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.000992

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461668

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000177

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000633

Hom.:

Bravo

AF:

0.000215

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000123

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 10, 2024

The c.427A>G (p.N143D) alteration is located in exon 3 (coding exon 2) of the SLC46A3 gene. This alteration results from a A to G substitution at nucleotide position 427, causing the asparagine (N) at amino acid position 143 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.049

T;T

MetaSVM

Uncertain

-0.11

MutationAssessor

Benign

1.5

L;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.60

N;N

REVEL

Uncertain

0.35

Sift

Benign

0.48

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.99

D;D

Vest4

0.33

MVP

0.59

MPC

0.57

ClinPred

0.090

GERP RS

6.2

Varity_R

0.098

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over